A method of increasing the hydrophilicity of an implant to be implanted into living bone. The method comprises the act of depositing non-toxic salt residuals on the surface of the implant by exposing the surface to a solution including the non-toxic salts. The method further comprises the act of drying the implant.
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1. A method of forming an implant to be implanted into living bone, the method comprising the acts of:
roughening at least a portion of the implant surface to form a roughened surface; and
increasing the hydrophilicity of the roughened surface by depositing at least one non-toxic salt residual on the roughened surface, the at least one non-toxic salt residual including sodium lactate.
13. A dental implant comprising:
a head portion having a non-rotational feature;
a lowermost end opposing the head portion; and
a threaded bottom portion for engaging bone between the head portion and the lowermost end, the threaded bottom portion having a roughened surface with an array of microscale irregularities, the threaded bottom portion further including discrete non-toxic salt residuals located on the roughened surface, the discrete non-toxic salt residuals including sodium lactate.
5. A dental implant comprising:
a head portion having a non-rotational feature;
a lowermost end opposing the head portion; and
a threaded bottom portion for engaging bone between the head portion and the lowermost end, the threaded bottom portion having a roughened surface with an array of microscale irregularities, the threaded bottom portion further including at least one non-toxic salt residual located on the roughened surface, the at least one non-toxic salt residual including sodium lactate.
2. The method of
3. The method of
4. The method of
6. The implant of
7. The dental implant of
8. The dental implant of
9. The dental implant of
10. The dental implant of
11. The dental implant of
14. The dental implant of
15. The dental implant of
16. The dental implant of
17. The dental implant of
18. The dental implant of
19. The dental implant of
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This application is a continuation of U.S. patent application Ser. No. 13/648,837, filed Oct. 10, 2012 (now U.S. Pat. No. 8,852,672) which is a continuation of U.S. patent application Ser. No. 12/359,780, filed Jan. 26, 2009 (now U.S. Pat. No. 8,309,162) which claims the benefit of U.S. Provisional Application No. 61/137,293, filed Jul. 28, 2008 and U.S. Provisional Application No. 61/062,577, filed Jan. 28, 2008, which are hereby incorporated by reference in their entireties.
This invention relates generally to implants and, in particular, to a dental implant having salt residuals deposited thereon and methods of making the same.
It is becoming more common to replace a missing tooth with a prosthetic tooth that is placed upon and attached to a dental implant. Dental implants are often comprised of metal and metal alloys, including titanium (Ti) and titanium alloys. The dental implant serves as an artificial root that integrates with the bone tissue of the mouth below the gingiva.
For the dental implant to function successfully, sufficient osseointegration is required. In other words, a direct chemical bond between the implant and the bone must be formed and retained. Osseointegration materials may be incorporated onto the surface of the implant to help enhance the osseointegration process. Non-limiting examples of osseointegration materials include calcium phosphate ceramic materials such as hydroxyapatite, which is particularly chemically stable and osseoconductive.
To provide sufficient long-term behavior of an implant having an osseointegration compound on the surface, there must be a sufficient bond strength between the implant and the compound. Moreover, the compound is desirably sufficiently biostable such that the rate of dissolution of the compound is low.
The present invention is directed to an improved implant having salt residual deposits deposited on the implant surface for increasing the rate and extent of osseointegration and methods of forming the same.
The present invention relates to a method of increasing the hydrophilicity of an implant to be implanted into living bone. The method comprises the act of depositing non-toxic salt residuals on the surface of the implant by exposing the surface to a solution including the non-toxic salts. The method further comprises the act of drying the implant.
According to another process of the present invention, a method of forming an implant to be implanted into living bone comprises the act of roughening at least a portion of the implant surface to form a roughened surface. The method further comprises the act of increasing the hydrophilicity of the roughened surface by depositing non-toxic salt residuals on the roughened surface by exposing the roughened surface to a solution including the non-toxic salt.
According to another process of the present invention, a method of forming a dental implant made of titanium or titanium alloy comprises the act of removing a native oxide layer from a threaded bottom portion of the dental implant. The method further comprises the act of acid etching the threaded bottom portion to form a roughened surface having an array of micro scale irregularities having peak-to-valley heights not greater than about 20 microns. The method further comprises the act of depositing discrete hydroxyapatite nanocrystals on the roughened surface by exposure to a solution comprising 2-methoxyethanol solvent and the hydroxyapatite nanocrystals. The method further comprises the act of depositing salt residuals on the roughened surface by exposure to a solution comprising non-toxic salts. The salt residuals increase the hydrophilicity of the implant surface.
According to one embodiment of the present invention, a dental implant comprises a head portion having a non-rotational feature. The dental implant further comprises a lowermost end opposing the head portion. The dental implant further comprises a threaded bottom portion for engaging bone between the head portion and the lowermost end. The threaded bottom portion has a roughened surface with an array of microscale irregularities having peak-to-valley heights not greater than about 20 microns. The threaded bottom portion further includes discrete nanoparticles located on the roughened surface. The nanoparticles include hydroxyapatite nanocrystals. The threaded bottom portion further includes salt residuals deposited thereon.
According to another process of the present invention, a method of increasing the hydrophilicity of an implant to be implanted into living bone comprises the act of depositing non-toxic salt residuals on the surface of the implant by immersing at least a portion of the implant in a solution including sodium chloride, potassium chloride, calcium chloride, sodium lactate, or combinations thereof. The method further comprises the act of drying the implant. The contact angle formed by a deionized water droplet on the surface of the implant ranges from about 5° to about 65°.
According to another process of the present invention, a method of forming an implant to be implanted into living bone is disclosed. The method comprises the act of grit blasting at least a portion of the implant surface with a grit blast media. The method further comprises the act of removing residual grit blast media. The method further comprises the act of roughening the grit blasted portion of the implant surface to form a roughened surface. The method further comprises the act of depositing discrete hydroxyapatite nanocrystals on the roughened surface. The method further comprises the act of optionally increasing the hydrophilicity of the roughened surface by depositing non-toxic salt residuals on the roughened surface by exposing the roughened surface to a solution including the non-toxic salt.
The above summary of the present invention is not intended to represent each embodiment, or every aspect, of the present invention. This is the purpose of the figures and the detailed description which follow.
The foregoing and other advantages of the invention will become apparent upon reading the following detailed description and upon reference to the drawings.
The present invention is directed to implants having salt residuals deposited thereon and methods of making the same. The salt residuals have been shown to increase the hydrophilicity (i.e., wettability) of the implant surface, thereby assisting in increasing the rate and extent of osseointegration with bone. An implant in the context of the present invention means a device intended to be placed within a human body such as to connect skeletal structures (e.g., a hip implant) or to serve as a fixture for a body part (e.g., a fixture for an artificial tooth). Although the remainder of this application is directed to a dental implant, it is contemplated that the present invention may also be applied to other (e.g., medical) implants.
In the implant 10 of
The exterior of the threaded bottom portion 16 facilitates bonding with bone or gingiva. The threaded bottom section 16 includes a thread 18 that makes a plurality of turns around the implant 10. The threaded bottom portion 16 may further include a self-tapping region with incremental cutting edges 17 that allows the implant 10 to be installed without the need for a bone tap. Examples of incremental cutting edges 17 are described in detail in U.S. Pat. No. 5,727,943, entitled “Self-Tapping, Screw-Type Dental Implant,” which is incorporated by reference in its entirety.
In
According to the present invention, a controlled deposition of salt residuals overlies at least a portion (e.g., the threaded bottom portion) of the surface of an implant. Referring now to
Turning now to
Referring to
Referring to
Discrete nanoparticles comprising a material promoting osseointegration are then deposited on the roughened surface of the implant at step s306. In one embodiment, the nanoparticles include hydroxyapatite (HA) nanocrystals. The HA nanocrystals may be on the order of about 20 nanometers to about 100 nanometers. The discrete HA nanocrystals may be deposited onto the roughened surface by exposing the implant to a solution comprising 2-methoxyethanol solvent and HA nanocrystals. This type of deposition process is described in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, which have been incorporated by reference herein in their entireties.
Salt residuals are then deposited onto the surface of the implant at step s310. The salt residuals may include, but are not limited to, sodium chloride, potassium chloride, calcium chloride, and sodium lactate. The salt residuals may be introduced onto the surface of the implant by dipping or immersing the implant in a non-toxic salt solution. The non-toxic salt solution may, for example, be physiological saline solution or lactated Ringer's solution. The implant is then dried at step s314. The drying process may be conducted at ambient temperatures or at elevated temperatures. Additional acts may then be performed including, but not limited to, sterilization (e.g., gamma sterilization) and packaging.
According to another method of the present invention, salt residuals are deposited onto an implant surface having nanoparticles of a material promoting osseointegration (e.g., HA nanocrystals) deposited thereon, where the nanoparticles were deposited on the implant surface without first roughening the surface of the implant.
Referring to
Blast media residuals are then removed from the implant surface at step s404. The blast media residuals may be removed by, for example, exposing the implant to an acid (e.g., nitric acid) or acid solution.
At optional step s406, the implant surface is exposed to a first acid solution, which may include hydrofluoric acid, to prepare the implant for micron-scale etching (i.e., step s408). The first acid solution assists in cleaning the grit blasted implant surface and smoothening irregularities (e.g., from the implant machining process) thereon. The first acid solution also assists in removing any native oxide that may have reformed on the implant surface. It has been found that step s406 may be desirable for implants made of commercially pure (CP) titanium and may be eliminated for implants made of titanium alloy (e.g., titanium 6AL-4V ELI).
At step s408, The implant surface is then acid etched in a second acid solution to form a roughened surface including a substantially uniform array of microscale irregularities for enhancing the integration of the implant with bone or other biological interfaces. The acid etching step s408 imparts a separate micron level topography including average peak-to-peak distances of about 1 micron to about 3 microns. As described above with respect to step s302 of
As described above with respect to step s306 of
The implant surface may be characterized utilizing Field Emission Scanning Electron microscopy (FESEM). Depending upon the resolution of the instrument, the surface of the implant may typically be witnessed at magnifications of 10kX of greater. In the examples provided below, the SEM model was the JSM 6460LV (JEOL USA Inc., Peabody, Mass.), and the images were taken at 10kX magnification.
The changes in the surface chemistry of the implants may be analyzed by electron dispersion spectroscopy (EDS). In the examples below, an Oxford Instruments EDS (Oxfordshire, United Kingdom) was used. Additionally, the data provided in the tables of the examples below was obtained by analyzing and averaging two 100×200 micron spots of the respective titanium 6AL-4V ELI alloy disks.
The effect of the salt residuals on the hydrophilicty of the implants may be verified by measuring contact angles. The contact angle is a quantitative measure of the spread of a droplet on the surface, and is subsequently a measurement of its hydrophilicity. A smaller contact angle represents a more hydrophilic surface. In the examples below, a deionized water drop was injected onto the disk surfaces. The reaction of the droplet with the surface was recorded via imaging. During review of the imaging, the contact angle of the water on the disk surface was measured. The instrument used to measure the contact angles was an MD-OCA contact angle meter (Future Scientific, New York, N.Y.) using SCA20 software (DataPhysics, Germany).
Fifteen titanium 6AL-4V ELI alloy disks were machined using typical turning techniques. After machining, the disks were cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The disks were then rinsed thoroughly with deionized water and oven dried.
The fifteen titanium 6AL-4V ELI alloy disks were then separated into three groups. Group 1 included five disks and was utilized as a control group. Group 2 included five disks that were immersed in physiological saline solution (about 0.9 w/w % NaCl). After being soaked in the physiological saline solution for about five minutes, the disks were oven dried utilizing a forced convection oven at a temperature of about 100° C. Group 3 included five disks that were immersed in lactated Ringer's solution (about 0.6 w/w % NaCl, about 0.3 w/w % C5H5NaO3, about 0.03 w/w % KCl, and about 0.02 w/w % CaCl2). After being soaked in the lactated Ringer's solution for about five minutes, the disks were oven dried utilizing a forced convection oven at 100° C. The disks were then packaged in polyethylene zip-lock type bags.
One disk from each of the three groups was then analyzed using EDS to determine changes in the surface chemistry. The results are summarized in Table 1 below.
TABLE 1
Group 1 -
Group 2 -
Group 3 -
Control
Physiological Saline
Lactated Ringer's
(w/w %), n = 2
(w/w %), n = 2
(w/w %), n = 2
Titanium
87.87
79.85
43.58
Vanadium
3.84
2.1
0
Aluminum
6.28
5.4
3.06
Oxygen
0
0
14.86
Carbon
2.01
1.04
11.79
Calcium
0
0
0
Phosphorous
0
0
0
Sodium
0
5.67
12.94
Chloride
0
5.95
13.48
Potassium
0
0
0.305
Total
100
100
100
As shown in Table 1, the surface of the disk of the control group (Group 1) did not include any salt residuals, while the surfaces of the disks of Groups 2 and 3 included salt residuals. More specifically, the surface of the disk that was immersed in physiological saline solution (Group 2) included 5.67 w/w % sodium and 5.95 w/w % chloride (total: 11.62 w/w % salts). The surface of the disk that was immersed in lactated Ringer's solution (Group 3) included 14.86 w/w % oxygen, 11.79 w/w % carbon, 12.94 w/w % sodium, 13.48 w/w % chloride, and 0.305 w/w % potassium (total: 53.375 w/w %).
The same disks were then imaged using an FESEM to show the variations in the surface chemistry of the various disks.
Contact angles were then measured on each side of four disks from each group. The results are included in Table 2 below.
TABLE 2
Group 1 -
Group 2 -
Group 3 -
Control
Physiological Saline
Lactated Ringer's
Sample
(degrees)
(degrees)
(degrees)
1
86
68
18
2
80
57
32
3
76
76
21
4
87
77
30
5
85
73
31
6
82
79
31
7
81
70
49
8
78
59
28
Mean
81.9
69.9
30.0
SD
3.9
8.2
9.2
As shown in Table 2, the disks having salts deposited thereon—those of Groups 2 and 3—had the lowest contact angles (69.9° and 30.0°, respectively) and thus, were the most hydrophilic. Furthermore, the disks of Group 3, which were immersed in lactated Ringer's solution, were determined to be considerably more hydrophilic than the disks of Group 2, which were immersed in physiological saline solution. The disks of the control group, Group 1, which did not have any salt residuals deposited thereon, had the highest contact angles and, thus, were the least hydrophilic.
Fifteen titanium 6AL-4V ELI alloy disks were machined using typical turning techniques. After machining, the disks were cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The disks were then rinsed thoroughly with deionized water and oven dried. After oven drying, the disks were roughened using a dual acid etching process, described in U.S. Pat. App. Pub. No. 2004/0265780, which has been incorporated by reference herein, to produce an Osseotite® surface. The roughening process resulted in irregularities having peak-to-valley heights of no more than 10 microns. The disks were then oven dried.
The fifteen Osseotite® titanium 6AL-4V ELI alloy disks were then separated into three groups. Group 1 included five disks and was utilized as a control group. Group 2 included five disks that were immersed in physiological saline solution for about five minutes and then oven dried utilizing a forced convection oven at a temperature of 100° C. Group 3 included five disks that were immersed in lactated Ringer's solution for about five minutes and then oven dried utilizing a forced convection oven at 100° C. The disks were then packaged in polyethylene zip-lock type bags.
One disk from each of the three groups was then analyzed using EDS to determine changes in the surface chemistry. The results are summarized in Table 3 below.
TABLE 3
Group 1 -
Group 2 -
Group 3 -
Control
Physiological Saline
Lactated Ringer's
(w/w %), n = 2
(w/w %), n = 2
(w/w %), n = 2
Titanium
88.83
61.2
53.42
Vanadium
4.58
4.53
2.51
Aluminum
5.87
4.48
3.77
Oxygen
0
0
10.86
Carbon
0.73
3.91
8.1
Calcium
0
0
0
Phosphorous
0
0
0
Sodium
0
11.87
10.36
Chloride
0
14.02
10.99
Potassium
0
0
0
Total
100
100
100
As shown in Table 3, the surface of the disk of the control group, Group 1, did not include any salt residuals, while the surfaces of the disks of Groups 2 and 3 did include salt residuals. More specifically, the surface of the disk that was immersed in physiological saline solution (Group 2) included 11.87 w/w % sodium, and 14.02 w/w % chloride (total: 25.89 w/w % salts). The surface of the disk that was immersed in lactated Ringer's solution (Group 3) included 10.86 w/w % oxygen, 8.1 w/w % carbon, 10.36 w/w % sodium and 10.99 w/w % chloride (total: 40.31 w/w %).
The same disks analyzed in Table 3 were then imaged using an FESEM to show the variations in the surface chemistry of the various disks.
Contact angles were then measured on each side of four disks from each group. The results are included in Table 4 below.
TABLE 4
Group 1 -
Group 2 -
Group 3 -
Control
Physiological Saline
Lactated Ringer's
Sample
(degrees)
(degrees)
(degrees)
1
90
58
10
2
93
60
9
3
94
65
12
4
96
53
11
5
86
56
7
6
85
60
8
7
82
59
8
8
82
61
12
Mean
88.5
59.0
9.6
SD
5.5
3.5
1.9
The results of Table 4 were consistent with the data of Table 2 of Example 1 above. Specifically, the disks having salts deposited thereon—those of Groups 2 and 3—had the lowest contact angles and, thus, were the most hydrophilic. Furthermore, the disks of Group 3, which were immersed in lactated Ringer's solution, were determined to be considerably more hydrophilic than the disks of Group 2, which were immersed in physiological saline solution. The disks of the control group, Group 1, which did not have any salt residuals deposited thereon, had the highest contact angles and, thus, were the least hydrophilic.
Furthermore, comparing the contact angle measurements of Table 4 to those in Table 2 of Example 1 above shows that the contact angles of the disks that were roughened prior to immersion in the salt solution (i.e., those of Example 2) had generally lower contact angles and were, thus, more hydrophilic than the disks that were not roughened (i.e., those of Example 1).
Fifteen titanium 6AL-4V ELI alloy disks were machined using typical turning techniques. After machining, the disks were cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The disks were then rinsed thoroughly with deionized water and oven dried. After oven drying, the disks were roughened using the dual acid-etched process described in U.S. Pat. App. Pub. No. 2004/0265780, which has been incorporated by reference herein. Discrete crystals of hydroxyapatite were then deposited on the roughened surfaces of the disks using the process described in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, which have been incorporated by reference herein, to produce a Biomet 3i NanoTite™ surface. The disks were then oven dried.
The fifteen Biomet 3i NanoTite™ titanium 6AL-4V ELI alloy disks were then separated into three groups. Group 1 included five disks and was utilized as a control group. Group 2 included five disks that were immersed in physiological saline solution for about five minutes and then oven dried utilizing a forced convection oven at a temperature of 100° C. Group 3 included five disks that were immersed in lactated Ringer's solution for about five minutes and then oven dried utilizing a forced convection oven at 100° C. The disks were then packaged in polyethylene zip-lock type bags.
One disk from each of the three groups was then analyzed using EDS to determine changes in the surface chemistry. The results are summarized in Table 5 below.
TABLE 5
Group 1 -
Group 2 -
Group 3 -
Control
Physiological Saline
Lactated Ringer's
(w/w %)
(w/w %)
(w/w %)
Titanium
82.86
74.55
62.18
Vanadium
1.64
4.06
3.52
Aluminum
5.28
5.03
4.13
Oxygen
6.9
5.10
15.67
Carbon
1.45
1.71
5.80
Calcium
1.22
0.71
1.08
Phosphorous
0.67
0.31
0.15
Sodium
0
4.24
4.17
Chloride
0
4.32
2.90
Potassium
0
0
0.41
Total
100
100
100
As shown in Table 5, the surface of the disk of the control group (Group 1) did not include any salt residuals (except calcium and phosphate, which resulted from the deposition of discrete hydroxyapatite crystals), while the surfaces of the disks of Groups 2 and 3 included salt residuals. More specifically, the surface of the disk that was immersed in physiological saline solution (Group 2) included 4.24 w/w % sodium and 4.32 w/w % chloride (total: 8.56 w/w % sodium and chloride salts) that were not included in the control group (Group 1). The surface of the disk that was immersed in lactated Ringer's solution (Group 3) included 4.17 w/w % sodium, 2.90 w/w % chloride, and 0.41 w/w % potassium (total: 7.48 w/w % sodium, chloride, and potassium salts) that were not included in the control group (Group 1). Group 3 also included 15.67 w/w % oxygen and 5.80 w/w % carbon, which are directly related to the lactate salt (NaC3H5O3).
The same disks were then imaged using an FESEM to show the variations in the surface chemistry of the various disks.
Contact angles were then measured on each side of four disks from each group. The results of this testing are included in Table 6 below.
TABLE 6
Group 2 -
Group 3 -
Group 1 -
Physiological Saline
Lactated Ringer's
Sample
Control (degrees)
(degrees)
(degrees)
1
78
50
10
2
81
63
7
3
74
68
15
4
76
65
13
5
85
66
5
6
91
55
5
7
80
59
8
8
78
60
5
Mean
80.4
60.8
8.5
SD
5.4
6.0
3.9
The results of Table 6 were consistent with the data of Tables 2 and 4 of Example 1 and 2, respectively, above. Specifically, the disks having salts deposited thereon—those of Groups 2 and 3—had the lowest contact angles and, thus, were the most hydrophilic. Furthermore, consistent with the data of Table 4 above, the disks that were immersed in lactated Ringer's solution (Group 3) were determined to be considerably more hydrophilic than the disks that were immersed in physiological saline solution (Group 2). The disks that did not have any salt residuals deposited thereon (Group 1) had the highest contact angles and, thus, were the least hydrophilic.
The contact angles and the corresponding hydrophilicity of the disks of Groups 2 and 3 of the present example (having Biomet 3i NanoTite™ surfaces) are comparable to those of the disks of Groups 2 and 3 of Example 2 above (having only Osseotite® surfaces).
Since, as demonstrated in Examples 1-3 above, the lactated Ringer's solution salt residuals demonstrated a more robust effect on the initial hydrophilicity of the tested disk surfaces, an experiment was conducted to determine whether all of the constituents of the lactated Ringer's solution were causing the robust effect on hydrophilicity.
Thirty-five titanium 6AL-4V ELI alloy disks were machined using typical turning techniques. After machining, the disks were cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The disks were then rinsed thoroughly with deionized water and oven dried. After oven drying, the disks were roughened using the dual acid-etched process described in U.S. Pat. App. Pub. No. 2004/0265780, which has been incorporated by reference herein. Discrete crystals of hydroxyapatite were then deposited on the roughened surfaces of the disks using the process described in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, which have been incorporated by reference herein, to produce a Biomet 3i NanoTite™ surface. The disks were then oven dried.
The thirty-five Biomet 3i NanoTite™ titanium 6AL-4V ELI alloy disks were then separated into seven groups that included various concentrations of the components of lactated Ringer's solution. Group 1 included five disks and was utilized as a control group. Group 2 included five disks that were immersed in a solution of about 0.03 w/w % potassium chloride (KCl). Group 3 included five disks that were immersed in a solution of about 0.3 w/w % potassium chloride (KCl). Group 4 included five disks that were immersed in a solution of about 0.02 w/w % calcium chloride (CaCl2). Group 5 included five disks that were immersed in a solution of about 0.2 w/w % calcium chloride (CaCl2). Group 6 included five disks that were immersed in a solution of about 0.3 w/w % sodium lactate (C5H5NaO3). Group 7 included five disks that were immersed in a solution of about 3.0 w/w % sodium lactate (C5H5NaO3). After each group of disks was soaked in its respective solution for about five minutes, the disks were oven dried utilizing a forced convection oven at 100° C. The disks were then packaged in polyethylene zip-lock type bags.
One disk from each of the seven groups was then analyzed using EDS to determine changes in the surface chemistry. The results are summarized in Table 7 below.
TABLE 7
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
Group 7
Biomet 3i
0.03
0.3
0.02
0.2
0.3
3
NanoTite ™
w/w %
w/w %
w/w %
w/w %
w/w %
w/w %
Control
KCl
KCl
CaCl2
CaCl2
C5H5NaO3
C5H5NaO3
Titanium
82.86
83.65
68.20
86.39
52.05
75.35
54.77
Vanadium
1.64
4.31
2.88
2.41
0
0
1.43
Aluminum
5.28
5.63
4.73
5.58
3.60
3.53
3.66
Oxygen
6.90
3.59
0
3.51
31.08
12.89
25.32
Carbon
1.45
0
0
0
0
4.27
9.56
Calcium
1.22
0.53
1.56
1.13
7.16
1.31
0.78
Phosphorus
0.67
0.75
0.65
0
0
0.38
0.24
Sodium
0
0
0
0
0
2.28
4.26
Chloride
0
0.78
10.81
1.00
6.13
0
0
Potassium
0
0.77
11.20
0
0
0
0
Total
100
100
100
100
100
100
100
The same disks were then imaged using an FESEM to show the variations in the surface chemistry of the various disks.
Contact angles were then measured on each side of four disks from each group. The results are included in Table 8 below.
TABLE 8
Group 1-
Group 2-
Group 3-
Group 4-
Group 5-
Group 6-
Group 7-
Biomet 3i
0.03
0.3
0.02
0.2
0.31
3.1
NanoTite ™
w/w %
w/w %
w/w %
w/w %
w/w %
w/w %
Sample
Control
KCl
KCl
CaCl2
CaCl2
C5H5NaO3
C5H5NaO3
1
78
80
50
50
10
15
5
2
81
74
60
41
10
9
5
3
74
72
63
32
13
10
6
4
76
65
51
36
13
6
5
5
85
71
55
42
25
13
6
6
91
73
55
42
26
10
5
7
80
73
53
45
17
10
5
8
78
70
53
46
10
7
5
Mean
80.38
72.25
55.00
41.75
15.50
10.00
5.25
SD
5.42
4.20
4.44
5.68
6.61
2.93
0.46
As demonstrated in Tables 7 and 8, the results indicated that salt residuals were deposited on all of the disks and that all of the salt residuals tested increased the initial hydrophilicity of the dual acid etched (Osseotite®) and discrete crystal deposited (Biomet 3i NanoTite™) surfaces.
The above-described processes deposited salt residuals on a disk surface. These salt residuals are intended to be non-toxic and easily absorbed in aqueous media. The following experiment demonstrates the water soluble nature of the salt residuals.
Four titanium 6AL-4V ELI alloy disks were machined using typical turning techniques. The disks were pre-cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The disks were then rinsed thoroughly with deionized water and oven dried. After oven drying, the disks were roughened using the dual acid-etched process described in U.S. Pat. App. Pub. No. 2004/0265780, which has been incorporated by reference herein. Discrete crystals of hydroxyapatite were then deposited on the roughened surfaces of the disks using the process described in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, which have been incorporated by reference herein, to produce a Biomet 3i NanoTite™ surface. The disks were then dried.
The four titanium 6AL-4V ELI alloy disks were then separated into two groups. Group 1 included two disks that were immersed in physiological saline for about five minutes and then oven dried utilizing a forced convection oven at a temperature of 100° C. Group 2 included two disks that were immersed in lactated Ringer's solution for about five minutes and then oven dried utilizing a forced convection oven at 100° C.
The disks were then imaged using an FESEM to show the variations in the surface chemistry of the various disks.
Post analysis, the disks from each group were rinsed for 1 minute in stagnant deionized water at a pH ranging from about 6 to about 7.5 at a temperature of about 37° C. (to simulate standard human body temperature). After being rinsed, the disks were oven dried in a forced convection oven set at 100° C. and packaged in polyethylene zip-lock type bags.
The disks were subsequently re-imaged using an FESEM at 10kX magnification.
TABLE 9
Control
Group 1 -
Group 2 -
Group -
After 1 minute
Group 2 -
After 1 minute
Biomet 3i
Group 1 -
rinse,
Lactated
rinse, Lactated
NanoTite ™
Physiological
Physiological
Ringer's
Ringer's
Control
Saline (w/w %)
Saline (w/w %)
(w/w %)
(w/w %)
Titanium
82.86
74.55
82.64
62.18
82.65
Vanadium
1.64
4.06
4.33
3.52
4.31
Aluminum
5.28
5.03
5.575
4.13
5.63
Oxygen
6.90
5.10
4.58
15.67
4.15
Carbon
1.45
1.71
1.645
5.80
2.23
Calcium
1.22
0.71
0.875
1.08
0.76
Phosphorous
0.67
0.31
0.36
0.15
0.30
Sodium
0
4.24
0
4.17
0
Chloride
0
4.32
0
2.90
0
Potassium
0
0
0
0.41
0
Total
100
100
100
100
100
The qualitative images from the FESEM and quantitative results from the EDS (see Table 9) indicated that the 1 minute rinse was sufficient to remove the sodium, chloride, potassium, carbon, and oxygen residuals to typical pre-salt deposition levels. Thus, the salt residuals were shown to be water soluble and easily absorbed in aqueous media.
The above-described processes deposit non-toxic, soluble salt residues on the surface. The salt residues have been shown to increase the surface hydrophilicity (wettability). The following in-vivo experiment utilizing a rat demonstrates the effect of this surface enhancement and quantifies the strength of the interface between osseointegrated bone and implants including salt residues.
Thirty-six tensile strength titanium 6AL-4V ELI implants (6 mm×4 mm×1.5 mm) were machined using typical turning techniques. After machining, the implants were cleaned with an aqueous detergent including ultraonics to remove residual machining fluid. The implants were then rinsed thoroughly with deionized water and oven dried. After oven drying, the implants were roughened using the dual acid-etched process described in U.S. Pat. App. Pub. No. 2004/0265780, which has been incorporated by reference herein. Discrete crystals of hydroxyapatite were then deposited on the roughened surfaces of the implants using the process described in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, which have been incorporated by reference herein, to produce a Biomet 3i NanoTite™ surface. The disks were then dried.
The thirty-six implants were separated into three groups. Group 1 included twelve implants and was utilized as a control group. The implants of Group 1 underwent no further processing, with the exception of packaging in a nylon bag, appropriate labeling, and sterilizing via gamma irradiation. Group 2 included twelve implants that were immersed in lactated Ringer's solution and oven dried utilizing a forced convection oven at 100° C. The implants of Group 2 were then packaged in a nylon bag, appropriately labeled, and sterilized via gamma irradiation. Group 3 included twelve implants that were immersed in a solution including about 0.2 w/w % CaCl2 and oven dried utilizing a forced convection oven at 100° C. The implants of Group 3 were then packaged in a nylon bag, appropriately labeled, and sterilized via gamma irradiation. Lactated Ringer's solution was used to demonstrate the effect of an organic salt (sodium lactate). 0.2 w/w % CaCl2 solution was used to demonstrate the effect of a non-organic salt (calcium chloride). Additionally, the residuals from these salts exhibited increased surface wettability in the experiments described above.
The implants were placed antero-posteriorly into the distal metaphyses of both femora of male Wistar rats for nine days. The femora of the sacrificed animals were trimmed to the width of the implant and placed in sucrose buffer. The resulting samples included two cortical arches of bone attached to each implant. For each sample, nylon lines were passed through the marrow spaces between the implant and each cortical arch, and the implant was secured in a vice attached to an Instron® Universal Testing System (model 8501), manufactured by Instron Corporation® (Burlington, Ontario). Each nylon line was then attached to a frame of the Instron® machine and displaced at a crosshead speed of 30 mm/min. The amount of force required to rupture the sample was recorded. For each implant, two force/displacement results were generated, one for each femoral arch (medial and lateral). Thus, since each group included twelve implants, twenty-four force/displacement results were obtained for each group. The results are summarized in Table 10 below.
TABLE 10
Group 1
Group 2 - Lactated
Group 3 -
(control)
Ringer's solution)
0.2 w/w % CaCl2)
Mean Force (N)
12.61
14.73
11.28
Standard
5.37
5.07
6.34
Deviation
The implants from all three groups integrated well. This demonstrated that the addition of the saline residuals had no significant adverse effects on the integration of the implant with bone. In fact, the data indicated that the implants of Group 2 that were immersed in lactated Ringer's solution required about 17% more bone removal force as compared with the control group (p=0.083).
This in-vivo experiment demonstrated the safety of depositing saline residuals on the surface of implants and the potential benefit of select salts on the rate and extent of osseointegration.
While the present invention has been generally described relative to the part of the implant contacting bone tissue, it is contemplated that the acts of etching, acid etching, roughening, and depositing herein described may be performed on the entire implant.
While the present invention has been described with reference to one or more particular embodiments, those skilled in the art will recognize that many changes may be made thereto without departing from the spirit and scope of the present invention. Each of these embodiments and obvious variations thereof is contemplated as falling within the spirit and scope of the claimed invention, which is set forth in the following claims.
Mayfield, Robert L., Towse, Ross W., Marks, Jacqueline K.
| Patent | Priority | Assignee | Title |
| Patent | Priority | Assignee | Title |
| 3772355, | |||
| 3984914, | Jul 24 1974 | Oral implant | |
| 4097935, | Aug 02 1974 | SANOFI S A | Hydroxylapatite ceramic |
| 4131597, | Jan 17 1975 | Ernst Leitz GmbH | Bioactive composite material process of producing and method of using same |
| 4145764, | Jul 23 1975 | Sumitomo Chemical Co., Ltd.; Matsumoto Dental College | Endosseous implants |
| 4146936, | Dec 30 1975 | Sumitomo Chemical Company Limited | Implants for bones, joints and tooth roots |
| 4223412, | Dec 16 1976 | Sumitomo Chemical Company, Limited | Implants for bones, joints or tooth roots |
| 4321042, | Mar 16 1976 | Ceramic dental implant | |
| 4330891, | Mar 07 1979 | Element for implantation in body tissue, particularly bone tissue | |
| 4366183, | Jun 17 1980 | SOCIETE NATIONALE D ETUDE ET DE CONSTRUCTION DE MOTEURS D AVIATION | Process for making bioactive coatings on osseous prostheses, and prostheses thus obtained |
| 4403941, | Aug 06 1979 | Babcock-Hitachi, Ltd. | Combustion process for reducing nitrogen oxides |
| 4451235, | Oct 08 1978 | Kureha Kagaku Kogyo Kabushiki Kaisha | Process for preparing an artificial dental root |
| 4538306, | Jun 26 1982 | Feldmuhle Aktiengesellschaft | Implantable elbow joint |
| 4636526, | Feb 19 1985 | The Dow Chemical Company | Composites of unsintered calcium phosphates and synthetic biodegradable polymers useful as hard tissue prosthetics |
| 4687487, | Jul 21 1978 | ASSSOCIATION SUISSE POUR LA RECHERCHE HORLOGERE | Joint implant |
| 4746532, | Aug 08 1985 | Matsumoto Dental College | Method for the production of endosseous implants |
| 4818559, | Aug 08 1985 | Sumitomo Chemical Company, Limited | Method for producing endosseous implants |
| 4830993, | Jan 20 1986 | Solvay & Cie (Societe Anonyme) | Process for the manufacture of a metal oxide powder for ceramic materials and zirconia powder produced by this process |
| 4846837, | Feb 12 1986 | KSB PARTNERSHIP | Ceramic-coated metal implants |
| 4847163, | Oct 17 1986 | Permelec Electrode, Ltd. | Metal-metal oxide composites and a coating layer of calcium phosphate on the oxide layer |
| 4863474, | Jul 08 1983 | Zimmer Limited | Skeletal implants |
| 4871578, | Apr 04 1987 | MTU Motoren - und Turbinen-Union Munchen GmbH | Hydroxylapatite coating on metal or ceramic |
| 4879136, | Feb 24 1987 | DENTSPLY G M B H | Method of applying opaque dental ceramic material to a metal structure |
| 4880610, | Apr 20 1988 | Norian Corporation | In situ calcium phosphate minerals--method and composition |
| 4882196, | Mar 24 1986 | Permelec Electrode Ltd. | Process for the production of a titanium composite materials coated with calcium phosphate compound |
| 4904534, | Jun 10 1985 | Kureha Kagaku Kogyo Kabushiki Kaisha | Implant material |
| 4908030, | Apr 29 1987 | V P INTELLECTUAL PROPERTIES, L L C | Method of manufacturing synthetic bone coated surgical implants |
| 4909846, | Oct 31 1987 | E I DU PONT DE NEMOURS AND COMPANY | Compositions based on titanium chelates of diols and titanium acylates |
| 4911953, | Sep 29 1987 | Permelec Electrode Ltd. | Process for producing composite materials having a coating of calcium phosphate compound |
| 4929589, | Dec 29 1986 | Alcoa Inc | Metal oxide/hydroxide particles coated with phosphate esters |
| 4944754, | Apr 29 1987 | FIRST SOURCE FINANCIAL LLP | Method of manufacturing synthetic bone coated surgical implants |
| 4960646, | Mar 24 1986 | Permelec Electrode Ltd. | Titanium composite materials coated with calcium phosphate compound |
| 4965088, | Oct 17 1986 | Permelec Electrode Ltd. | Calcium phosphate-coated composite material and process for production thereof |
| 4969906, | Jul 28 1987 | Bone and bony tissue replacement | |
| 4988362, | Mar 30 1988 | Agency of Industrial Science & Technology, Ministry of International | Composition for coating bioceramics, method for coating bioceramics therewith, and composite bioceramics produced therewith |
| 4990163, | Feb 06 1989 | TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE, PHILADELPHIA, PA A NON-PROFIT CORP OF PA | Method of depositing calcium phosphate cermamics for bone tissue calcification enhancement |
| 5030474, | Dec 23 1987 | Sumitomo Chemical Company, Limited | Method for forming hydroxyapatite coating film using coating liquor containing hydroxyapatite |
| 5068122, | Mar 29 1989 | Kyoto University | Process for forming a bioactive hydroxyapatite film |
| 5071434, | Apr 20 1990 | NGK Spark Plug Co., Ltd. | Biologically active surface ceramic and process for producing the same |
| 5071436, | Jul 30 1985 | BASF Beauty Care Solutions France SAS | Substitute bony matrix products promoting osteogenesis |
| 5077132, | Oct 20 1986 | Shigeo, Maruno | Biocompatible composite material and a method for producing the same |
| 5092890, | Jan 12 1989 | BASF Aktiengesellschaft | Implant materials for hard tissue |
| 5128169, | Jan 08 1990 | Sumitomo Chemical Company, Limited | Method for forming hydroxyapatite coating film |
| 5134009, | Sep 15 1988 | Asahi Kogaku Kogyo K.K. | Shaped article of oriented calcium phosphate type compounds, sinter thereof and processes for producing same |
| 5141576, | Mar 24 1986 | Permelec Electrode, Ltd. | Titanium composite materials coated with calcium phosphate compound and process for production thereof |
| 5180426, | Dec 28 1987 | Asahi Kogaku Kogyo K.K. | Composition for forming calcium phosphate type setting material and process for producing setting material |
| 5185208, | Mar 06 1987 | Matsushita Electric Industrial Co., Ltd. | Functional devices comprising a charge transfer complex layer |
| 5188670, | Apr 05 1990 | KNC NOR ACQUISITION SUB, INC | Apparatus for hydroxyapatite coatings of substrates |
| 5196201, | Oct 20 1989 | GS DEVELOPMENT AB, A SWEDISH CORP | Implant material composition, preparation thereof as well as uses thereof and implant product obtainable therefrom |
| 5205921, | Feb 04 1991 | SHIRKHANZADEH, MORTEZA | Method for depositing bioactive coatings on conductive substrates |
| 5207705, | Dec 08 1988 | TRUDELL, LEONARD A ; WHITTEMORE, ANTHONY D | Prosthesis of foam polyurethane and collagen and uses thereof |
| 5219361, | Sep 16 1988 | Clemson University | Soft tissue implant with micron-scale surface texture to optimize anchorage |
| 5231151, | Jan 18 1991 | The Dow Chemical Company | Silica supported transition metal catalyst |
| 5263491, | May 12 1992 | Ambulatory metabolic monitor | |
| 5279720, | Nov 27 1991 | Minnesota Mining and Manufacturing Company | Electrophoretic deposition of transition metal dichalcogenides |
| 5279831, | Apr 05 1990 | Norian Corporation | Hydroxyapatite prosthesis coatings |
| 5286571, | Aug 21 1992 | Northwestern University | Molecular modification reagent and method to functionalize oxide surfaces |
| 5344457, | May 19 1986 | GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO, THE | Porous surfaced implant |
| 5344654, | Apr 08 1988 | Stryker Corporation | Prosthetic devices having enhanced osteogenic properties |
| 5358529, | Mar 05 1993 | Smith & Nephew Richards Inc. | Plastic knee femoral implants |
| 5397642, | Apr 28 1992 | The United States of America as represented by the United States | Articles including thin film monolayers and multilayers |
| 5456723, | Mar 23 1989 | STRAUMANN HOLDINGS AG; Straumann Holding AG | Metallic implant anchorable to bone tissue for replacing a broken or diseased bone |
| 5478237, | Feb 14 1992 | Nikon Corporation | Implant and method of making the same |
| 5484286, | Oct 08 1990 | Aktiebolaget Astra | Method for the preparation of implants made of titanium or alloys thereof |
| 5501706, | Nov 29 1994 | REGENTS OF THE UNIVERSITY OF MICHIGAN, THE | Medical implant structure and method for using the same |
| 5522893, | Mar 12 1993 | ADA Foundation | Calcium phosphate hydroxyapatite precursor and methods for making and using the same |
| 5527837, | Apr 25 1994 | Shin-Etsu Chemical Co., Ltd. | Heat-curable silicone elastomer compositions |
| 5543019, | Apr 23 1993 | Etex Corporation | Method of coating medical devices and device coated thereby |
| 5558517, | Feb 24 1992 | Clemson University | Polymeric prosthesis having a phosphonylated surface |
| 5571188, | Dec 04 1992 | Astra Aktiebolag | Process for treating a metallic surgical implant |
| 5584875, | Dec 20 1991 | C R BARD, INC | Method for making vascular grafts |
| 5603338, | Nov 30 1994 | Biomet 3i, LLC | Implant surface preparation utilizing acid treatment |
| 5609633, | Nov 09 1993 | SAGAWA PRINTING COMPANY LIMITED | Titanium-based bone-bonding composites having inverted concentration gradients of alkali and titanium ions in a surface layer |
| 5612049, | Apr 23 1992 | Vivoxid Oy | Bioactive coatings and their preparation and use |
| 5639402, | Aug 08 1994 | BioMedical Enterprises, Inc | Method for fabricating artificial bone implant green parts |
| 5652016, | Jul 27 1990 | Osaka Cement Co., Ltd. | Tetracalcium phosphate-based materials and processes for their preparation |
| 5683249, | Mar 22 1995 | Den-Mat Holdings LLC | Dental implant process and treated prosthetic |
| 5700289, | Oct 20 1995 | THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH | Tissue-engineered bone repair using cultured periosteal cells |
| 5722439, | Feb 26 1996 | Dental floss dispenser on card format | |
| 5726524, | May 31 1996 | Minnesota Mining and Manufacturing Company | Field emission device having nanostructured emitters |
| 5727943, | Jan 24 1996 | Biomet 3i, LLC | Self-tapping, screw-type dental implant |
| 5730598, | Mar 07 1997 | Zimmer Dental, Inc | Prosthetic implants coated with hydroxylapatite and process for treating prosthetic implants plasma-sprayed with hydroxylapatite |
| 5733564, | Apr 14 1993 | Leiras Oy | Method of treating endo-osteal materials with a bisphosphonate solution |
| 5759376, | Sep 07 1994 | Dot Dunnschicht- Und Oberflaechen-technologie GmbH | Method for the electrodeposition of hydroxyapatite layers |
| 5759598, | Jun 29 1994 | Nestec S.A. | Fermented food product for animals |
| 5763092, | Sep 15 1993 | Etex Corporation | Hydroxyapatite coatings and a method of their manufacture |
| 5766247, | Dec 10 1993 | Kabushiki Kaisya Advance | Process for producing a bioimbedding material |
| 5766669, | Aug 24 1995 | Warsaw Orthopedic, Inc | Sintering process for producing thin films of calcium phosphate entities |
| 5767032, | Dec 03 1993 | Borealis Technology Oy | Catalyst for olefin polymerization and a method for the manufacture thereof |
| 5772439, | Mar 28 1995 | Kanebo Limited; YAMAOKA, AKIRA; NISHIMURA, KAZUAKI | Hybrid dental implant |
| 5807430, | Nov 06 1995 | CHEMAT TECHNOLOGY, INC | Method and composition useful treating metal surfaces |
| 5811151, | May 31 1996 | Medtronic, Inc | Method of modifying the surface of a medical device |
| 5817326, | Dec 01 1995 | Los Alamos National Security, LLC | Processing of hydroxylapatite coatings on titanium alloy bone prostheses |
| 5820368, | Oct 23 1995 | ORTHOCLEAR HOLDINGS, INC | Disposable applicator for forming and retaining an orthodontic attachment |
| 5858318, | Nov 27 1996 | BERKELEY ADVANCED BIOMATERIALS, INC | Methods of synthesizing hydroxyapatite powders and bulk materials |
| 5871547, | Mar 01 1996 | Saint-Gobain Norton Industrial Ceramics Corporation | Hip joint prosthesis having a zirconia head and a ceramic cup |
| 5876453, | Nov 30 1994 | Biomet 3i, LLC | Implant surface preparation |
| 5902109, | Jan 18 1996 | Biomet 3i, LLC | Reduced friction screw-type dental implant |
| 5932299, | Apr 23 1996 | KT Holdings, LLC | Method for modifying the surface of an object |
| 5934287, | Sep 30 1996 | Brainbase Corporation | Implant with bioactive particles stuck and method of manufacturing the same |
| 5938435, | Jul 22 1997 | Orthodontic appliance shield system | |
| 5947893, | Apr 27 1994 | Board of Regents, The University of Texas System | Method of making a porous prothesis with biodegradable coatings |
| 5952399, | Sep 30 1996 | Degussa-Huls Aktiengesellschaft | Polymerisable dental material and use of apatite fillers in the dental material |
| 5958340, | Oct 21 1994 | Fraunhofer-Gesellschaft zur Foerderung der Angewandten Forschung E.V. | Solid-state chemical sensor |
| 5958504, | Sep 15 1993 | Etex Corporation | Hydroxyapatite coatings and a method of their manufacture |
| 5962549, | Nov 09 1995 | University of London; University of Florida Research Foundation | Bioactive composite material for repair of hard and soft tissues |
| 5981619, | Sep 14 1995 | Takiron Co., Ltd. | Material for osteosynthesis and composite implant material, and production processes thereof |
| 5990381, | Nov 13 1996 | ISE INTERNATIONAL, INC | Biomedical materials |
| 6013591, | Jan 16 1997 | Massachusetts Institute of Technology | Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production |
| 6051272, | Mar 15 1996 | Board of Trustees of the University of Illinois, The | Method for synthesizing organoapatites on to surgical metal alloys |
| 6069295, | May 10 1996 | OCTOPLUS SCIENCES B V | Implant material |
| 6077989, | May 28 1996 | 1208211 ONTARIO LIMITED | Resorbable implant biomaterial made of condensed calcium phosphate particles |
| 6129928, | Sep 05 1997 | ICET, INC | Biomimetic calcium phosphate implant coatings and methods for making the same |
| 6136369, | May 10 1996 | CHIENNA B V | Device for incorporation and release of biologically active agents |
| 6139585, | Mar 11 1998 | DEPUY PRODUCTS INC ; DEPUY PRODUCTS, INC | Bioactive ceramic coating and method |
| 6143037, | Jun 12 1996 | MICHIGAN, REGENTS, THE, UNIVERSITY OF | Compositions and methods for coating medical devices |
| 6143948, | May 10 1996 | CHIENNA B V | Device for incorporation and release of biologically active agents |
| 6146686, | May 10 1996 | OCTOPLUS SCIENCES B V | Implant material and process for using it |
| 6146767, | Oct 17 1996 | The Trustees of Princeton University | Self-assembled organic monolayers |
| 6153266, | Dec 08 1997 | JAPAN AS REPRESENTED BY DIRECTOR GENERAL OF AGENCY OF INDUSTRIAL SCIENCE AND TECHNOLOGY: TAKEO SATO; NGK SPARK PLUG CO , LTD | Method for producing calcium phosphate coating film |
| 6153664, | Apr 18 1997 | Cambridge Scientific, Inc. | Bioerodible polymeric semi-interpenetrating network alloys and internal fixation devices made therefrom |
| 6183255, | Mar 27 2000 | Titanium material implants | |
| 6190412, | Apr 22 1997 | Washington Research Foundation | Trap-coated bone grafts and prostheses |
| 6200137, | Jun 12 1997 | Ivoclar AG | Chemically stable translucent apatite glass ceramic |
| 6206598, | Sep 27 1999 | Capping device | |
| 6221111, | Dec 23 1996 | DR H C ROBERT MATHYS STIFTUNG | Bioactive surface layer for bone implants |
| 6261322, | May 14 1998 | SHALBY ADVANCED TECHNOLOGIES, INC | Implant with composite coating |
| 6270347, | Jun 10 1999 | Rensselaer Polytechnic Institute | Nanostructured ceramics and composite materials for orthopaedic-dental implants |
| 6280789, | Apr 30 1996 | BIOCOATINGS S R L | Process for preparation of hydroxyapatite coatings |
| 6280863, | Jun 12 1997 | Ivoclar AG | Translucent apatite glass ceramic |
| 6290982, | Dec 17 1996 | JVS-Polymers Oy | Plasticizable implant material and method for producing the same |
| 6306784, | Jun 12 1997 | IVOCLAR VIVADENT, INC | Alkali silicate glass |
| 6306925, | Dec 18 1998 | USBiomaterials Corporation | Tape cast multi-layer ceramic/metal composites |
| 6309660, | Jul 28 1999 | Edwards Lifesciences Corporation | Universal biocompatible coating platform for medical devices |
| 6338810, | Dec 23 1997 | Commissariat a l'Energie Atomique | Method for making apatite ceramics, in particular for biological use |
| 6344061, | May 10 1996 | CHIENNA B V | Device for incorporation and release of biologically active agents |
| 6344209, | Apr 24 1997 | Takeda Pharmaceutical Company, Limited | Apatite-coated solid composition |
| 6344276, | May 19 1999 | National Cheng Kung University | Non-dissolvable amorphous Ti-Ca-P coating for implant application |
| 6372354, | Sep 13 1999 | Chemat Technology, Inc. | Composition and method for a coating providing anti-reflective and anti-static properties |
| 6395299, | Feb 12 1999 | MOLECULAR INSIGHT PHARMACEUTICALS, INC | Matrices for drug delivery and methods for making and using the same |
| 6399215, | Mar 28 2000 | Triad National Security, LLC | Ultrafine-grained titanium for medical implants |
| 6419708, | Apr 30 1997 | Nobel Biocare Services AG | Calcium-phosphate coated implant element |
| 6426114, | May 02 2000 | The University of British Columbia | Sol-gel calcium phosphate ceramic coatings and method of making same |
| 6428803, | May 26 1998 | Hydroxylapatite gel | |
| 6508838, | Apr 22 1997 | Washington Research Foundation | Compositions for medical implantation |
| 6518328, | Dec 15 2000 | Biomet Manufacturing, LLC | Coated resorbable polymer and method of making the same |
| 6527849, | Jun 19 1990 | Self-repairing, reinforced matrix materials | |
| 6530958, | Oct 18 1993 | APRECIA PHARMACEUTICALS, LLC | Tissue regeneration matrices by solid free-form fabrication techniques |
| 6544732, | May 20 1999 | ILLUMINA, INC | Encoding and decoding of array sensors utilizing nanocrystals |
| 6569292, | Apr 04 2001 | Texas Christian University | Method and device for forming a calcium phosphate film on a substrate |
| 6569489, | Mar 11 1998 | DEPUY PRODUCTS INC ; DEPUY PRODUCTS, INC | Bioactive ceramic coating and method |
| 6589590, | Apr 06 1998 | Isis Innovation Limited | Composite material and methods of making the same |
| 6596338, | Oct 24 2001 | HOWMEDICA OSTEONICS CORP | Antibiotic calcium phosphate coating |
| 6617142, | Apr 25 1996 | Medtronic, Inc | Method for attachment of biomolecules to medical device surfaces |
| 6620861, | Nov 17 1999 | Kabushiki Kaisha Shofu | Dental fillers |
| 6645644, | Oct 17 1996 | TRUSTEES OF PRINCETON UNIVERSITY, THE | Enhanced bonding of phosphoric and phosphoric acids to oxidized substrates |
| 6652765, | Nov 30 1994 | Biomet 3i, LLC | Implant surface preparation |
| 6740366, | Dec 22 2000 | Nippon Sheet Glass Co., Ltd. | Article having predetermined surface shape and method for preparing the same |
| 6790455, | Sep 14 2001 | RESEARCH FOUNDATION AT STATE UNIVERSITY OF NEW YORK, THE | Cell delivery system comprising a fibrous matrix and cells |
| 6853075, | Jan 28 2003 | Wayne State University | Self-assembled nanobump array stuctures and a method to fabricate such structures |
| 6919070, | Oct 17 1997 | aap Biomaterials GmbH | Stomatic composition |
| 6960249, | Jul 14 1999 | VIVEX BIOLOGICS GROUP, INC | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface |
| 6969474, | Nov 30 1994 | Biomet 3i, LLC | Implant surface preparation |
| 6969501, | Jan 16 1997 | ORTHOVITA, INC | Minerals and methods for their production and use |
| 6991803, | Jan 26 1999 | ORTHOVITA, INC | Inorganic shaped bodies and methods for their production and use |
| 7007872, | Jan 03 2002 | PPG Industries Ohio, Inc | Methods for modifying the surface area of nanomaterials |
| 7018418, | Jan 25 2001 | TECOMET, INC | Textured surface having undercut micro recesses in a surface |
| 7067169, | Jun 04 2003 | Chemat Technology Inc. | Coated implants and methods of coating |
| 7067577, | Oct 16 2000 | Asahi Kasei Kabushiki Kaisha | Apatite-reinforced resin composition |
| 7083642, | Dec 22 2000 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| 7087086, | Jan 31 2003 | DePuy Products, Inc. | Biological agent-containing ceramic coating and method |
| 7105030, | May 14 1998 | CONSENSUS ORTHOPEDICS, INC | Implant with composite coating |
| 7112063, | Aug 11 2003 | 3M Innovative Properties Company | Dental implant system |
| 7169317, | Nov 30 1994 | Biomet 3i, LLC | Implant surface preparation |
| 7341756, | Jun 04 2003 | Chemat Technology, Inc. | Coated implants and methods of coating |
| 8029283, | Feb 28 2006 | Straumann Holding AG | Abutment with a hydroxylated surface |
| 8057843, | Aug 22 2006 | Thommen Medical AG | Implant, in particular dental implant |
| 8309162, | Jan 28 2008 | Biomet 3i, LLC | Implant surface with increased hydrophilicity |
| 8641418, | Mar 29 2010 | Biomet 3i, LLC | Titanium nano-scale etching on an implant surface |
| 8852672, | Jan 28 2008 | Biomet 3i, LLC | Implant surface with increased hydrophilicity |
| 9034201, | Mar 29 2010 | Biomet 3i, LLC | Titanium nano-scale etching on an implant surface |
| 20010020476, | |||
| 20020016635, | |||
| 20020018798, | |||
| 20020028424, | |||
| 20020119325, | |||
| 20020127391, | |||
| 20030005646, | |||
| 20030082232, | |||
| 20030099762, | |||
| 20030175773, | |||
| 20030219466, | |||
| 20030219562, | |||
| 20030231984, | |||
| 20040023048, | |||
| 20040024081, | |||
| 20040053197, | |||
| 20040053198, | |||
| 20040053199, | |||
| 20040083006, | |||
| 20040109937, | |||
| 20040121290, | |||
| 20040121451, | |||
| 20040145053, | |||
| 20040149586, | |||
| 20040210309, | |||
| 20040241613, | |||
| 20040249472, | |||
| 20040258726, | |||
| 20040265780, | |||
| 20050008620, | |||
| 20050014151, | |||
| 20050019365, | |||
| 20050031704, | |||
| 20050038498, | |||
| 20050100937, | |||
| 20050171615, | |||
| 20050211680, | |||
| 20050221072, | |||
| 20050226939, | |||
| 20050249654, | |||
| 20060039951, | |||
| 20060078587, | |||
| 20060105015, | |||
| 20060110306, | |||
| 20060141002, | |||
| 20060178751, | |||
| 20060229715, | |||
| 20060246105, | |||
| 20060257358, | |||
| 20060257492, | |||
| 20070010893, | |||
| 20070055254, | |||
| 20070110890, | |||
| 20070112353, | |||
| 20070173952, | |||
| 20070202144, | |||
| 20070202462, | |||
| 20070299535, | |||
| 20080044451, | |||
| 20080188938, | |||
| 20090132048, | |||
| 20100179665, | |||
| 20110104638, | |||
| 20110171602, | |||
| 20110233169, | |||
| 20130248487, | |||
| 20140034606, | |||
| DE3516411, | |||
| EP388576, | |||
| EP450939, | |||
| EP806212, | |||
| EP987031, | |||
| EP1053739, | |||
| EP1275422, | |||
| EP1847278, | |||
| GB2045083, | |||
| JP2000327515, | |||
| JP2018463, | |||
| JP5224448, | |||
| JP5228207, | |||
| JP523361, | |||
| WO44305, | |||
| WO137752, | |||
| WO203880, | |||
| WO220873, | |||
| WO3030957, | |||
| WO2006004778, | |||
| WO2006096793, | |||
| WO2006102347, | |||
| WO2007001744, | |||
| WO2007035217, | |||
| WO2007059038, | |||
| WO2007118734, | |||
| WO9513101, | |||
| WO9513102, | |||
| WO9639202, |
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